Properties of a tonically active, sodium-permeable current in mouse urinary bladder smooth muscle

2004 ◽  
Vol 286 (6) ◽  
pp. C1246-C1257 ◽  
Author(s):  
Kevin S. Thorneloe ◽  
Mark T. Nelson
Keyword(s):  
Membrane Potential ◽  
Urinary Bladder ◽  
Action Potential ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Bladder Smooth Muscle ◽  
Voltage Dependent ◽  
Urinary Bladder Smooth Muscle

Urinary bladder smooth muscle (UBSM) elicits depolarizing action potentials, which underlie contractile events of the urinary bladder. The resting membrane potential of UBSM is approximately −40 mV and is critical for action potential generation, with hyperpolarization reducing action potential frequency. We hypothesized that a tonic, depolarizing conductance was present in UBSM, functioning to maintain the membrane potential significantly positive to the equilibrium potential for K+ ( EK; −85 mV) and thereby facilitate action potentials. Under conditions eliminating the contribution of K+ and voltage-dependent Ca2+ channels, and with a clear separation of cation- and Cl−-selective conductances, we identified a novel background conductance ( Icat) in mouse UBSM cells. Icat was mediated predominantly by the influx of Na+, although a small inward Ca2+ current was detectable with Ca2+ as the sole cation in the bathing solution. Extracellular Ca2+, Mg2+, and Gd3+ blocked Icat in a voltage-dependent manner, with Ki values at −40 mV of 115, 133, and 1.3 μM, respectively. Although UBSM Icat is extensively blocked by physiological extracellular Ca2+ and Mg2+, a tonic, depolarizing Icat was detected at −40 mV. In addition, inhibition of Icat demonstrated a hyperpolarization of the UBSM membrane potential and decreased the amplitude of phasic contractions of isolated UBSM strips. We suggest that Icat contributes tonically to the depolarization of the UBSM resting membrane potential, facilitating action potential generation and thereby a maintenance of urinary bladder tone.

Ca(2+)-activated K+ channels regulate action potential repolarization in urinary bladder smooth muscle

1997 ◽  
Vol 273 (1) ◽  
pp. C110-C117 ◽  
Author(s):  
T. J. Heppner ◽  
A. D. Bonev ◽  
M. T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Action Potential ◽  
Single Channel ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Bladder Smooth Muscle ◽  
Apparent Dissociation Constant ◽  
K Channels ◽  
Urinary Bladder Smooth Muscle

The goal of this study was to examine the role of large conductance Ca(2+)-activated K+ channels in the regulation of cell excitability in urinary bladder smooth muscle from the guinea pig. Ca(2+)-activated K+ channels were studied with single-channel recording techniques and found to be intracellular Ca2+ and voltage dependent and sensitive to external tetraethylammonium and blocked by nanomolar concentrations of iberiotoxin (apparent dissociation constant of 4 nM). Spontaneous action potentials recorded from intact tissue strips depended on external Ca2+ and were inhibited by Ca2+ channel blockers. Iberiotoxin (100 nM) significantly altered the configuration of the action potential by increasing the duration and peak amplitude of the action potential and decreasing the rate of decay. Iberiotoxin also increased the action potential frequency from 0.11 to 0.29 Hz. This study suggests that Ca(2+)-activated K+ channels play a significant role in the repolarization of the action potential and in the maintenance of the resting membrane potential of the urinary bladder smooth muscle.

Identification of a spontaneously active, Na+-permeable channel in guinea pig gallbladder smooth muscle

2005 ◽  
Vol 289 (3) ◽  
pp. G501-G507 ◽  
Author(s):  
Georgi V. Petkov ◽  
Onesmo B. Balemba ◽  
Mark T. Nelson ◽  
Gary M. Mawe
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Guinea Pig ◽  
Action Potential ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Membrane Hyperpolarization ◽  
Permeable Channel

The action potential in gallbladder smooth muscle (GBSM) is caused by Ca2+ entry through voltage-dependent Ca2+ channels (VDCC), which contributes to the GBSM contractions. Action potential generation in GBSM is critically dependent on the resting membrane potential (about −50 mV), which is ∼35 mV more positive of the K+ equilibrium potential. We hypothesized that a tonic, depolarizing conductance is present in GBSM and contributes to the regulation of the resting membrane potential and action potential frequency. GBSM cells were isolated from guinea pig gallbladders, and the whole cell patch-camp technique was used to record membrane currents. After eliminating the contribution of VDCC and K+ channels, we identified a novel spontaneously active cation conductance ( Icat) in GBSM. This Icat was mediated predominantly by influx of Na+. Na+ substitution with N-methyl-d-glucamine (NMDG), a large relatively impermeant cation, caused a negative shift in the reversal potential of the ramp current and reduced the amplitude of the inward current at −50 mV by 65%. Membrane potential recordings with intracellular microelectrodes or in current-clamp mode of the patch-clamp technique indicated that the inhibition of Icat conductance by NMDG is associated with membrane hyperpolarization and inhibition of action potentials. Extracellular Ca2+, Mg2+, and Gd3+ attenuated the Icat in GBSM. Muscarinic stimulation did not activate the Icat. Our results indicate that, in GBSM, an Na+-permeable channel contributes to the maintenance of the resting membrane potential and action potential generation and therefore plays a critical role in the regulation of GBSM excitability and contractility.

scholarly journals Differential Contribution of Sodium Channel Subtypes to Action Potential Generation in Unmyelinated Human C-type Nerve Fibers

2007 ◽  
Vol 107 (3) ◽  
pp. 495-501 ◽  
Author(s):  
Philip M. Lang ◽  
Verena B. Hilmer ◽  
Peter Grafe
Keyword(s):  
Action Potential ◽  
Sodium Channels ◽  
Action Potentials ◽  
Peak Height ◽  
Nerve Fibers ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Compound C ◽  
C Fiber ◽  
Voltage Dependent

Background Multiple voltage-dependent sodium channels (Na(v)) contribute to action potentials and excitability of primary nociceptive neurons. The aim of the current study was to characterize subtypes of Na(v) that contribute to action potential generation in peripheral unmyelinated human C-type nerve fibers. Methods Registration of C-fiber compound action potentials and determination of membrane threshold was performed by a computerized threshold tracking program. Nerve fibers were stimulated with a 1-ms current pulse either alone or after a small ramp current lasting 300 ms. Results Compound C-fiber action potentials elicited by supramaximal 1-ms current pulses were rather resistant to application of tetrodotoxin (30-90 nM). However, the same concentrations of tetrodotoxin strongly reduced the peak height and elevated membrane threshold of action potentials evoked at the end of a 300-ms current ramp. A similar effect was observed during application of lidocaine and mexiletine (50 microM each). Conclusions These data indicate that more than one type of Na(v) contributes to the generation of action potentials in unmyelinated human C-type nerve fibers. The peak height of an action potential produced by a short electrical impulse is dependent on the activation of tetrodotoxin-resistant ion channels. In contrast, membrane threshold and action potential peak height at the end of a slow membrane depolarization are regulated by a subtype of Na(v) with high sensitivity to low concentrations of tetrodotoxin, lidocaine, and mexiletine. The electrophysiologic and pharmacologic characteristics may indicate the functional activity of the Na(v) 1.7 subtype of voltage-dependent sodium channels.

Disinhibition in cat motor cortex by ammonia

1975 ◽  
Vol 38 (2) ◽  
pp. 347-355 ◽  
Author(s):  
W. Raabe ◽  
R. J. Gumnit
Keyword(s):  
Membrane Potential ◽  
Motor Cortex ◽  
Action Potentials ◽  
Pyramidal Tract ◽  
Ammonium Salts ◽  
Resting Membrane Potential ◽  
Intracellular Recordings ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Postsynaptic Inhibition

The effect of intravenously administered ammonium salts on postsynaptic inhibition of pyramidal tract cells was investigated in cat motor cortex. Extracellular recordings revealed that pyramidally or thalamically mediated inhibition of antidromic action potentials is abolished by ammonia. Intracellular recordings demonstrated that hyperpolarizing IPSPs vanished and EPSPs appeared while the inhibitory stimuli still triggered a decrease of neuronal resistance and the resting membrane potential was unchanged. It is concluded that ammonia disinhibited action-potential generation and EPSPs by shifting E(IPSP) to the level of the resting membrane potential. With disinhibition and facilitation replacing inhibitation of action potentials, ammonia clearly disturbs those cortical functions involving postsynaptic inhibition.

scholarly journals Voltage-gated K+ channels sensitive to stromatoxin-1 regulate myogenic and neurogenic contractions of rat urinary bladder smooth muscle

2010 ◽  
Vol 299 (1) ◽  
pp. R177-R184 ◽  
Author(s):  
Muyan Chen ◽  
Whitney F. Kellett ◽  
Georgi V. Petkov
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Electrical Field Stimulation ◽  
Resting Membrane Potential ◽  
Bladder Smooth Muscle ◽  
Membrane Excitability ◽  
Molecular Fingerprints ◽  
Rat Urinary Bladder ◽  
Voltage Gated ◽  
Urinary Bladder Smooth Muscle

Members of the voltage-gated K+ (KV) channel family are suggested to control the resting membrane potential and the repolarization phase of the action potential in urinary bladder smooth muscle (UBSM). Recent studies report that stromatoxin-1, a peptide isolated from tarantulas, selectively inhibits KV2.1, KV2.2, KV4.2, and KV2.1/9.3 channels. The objective of this study was to investigate whether KV channels sensitive to stromatoxin-1 participate in the regulation of rat UBSM contractility and to identify their molecular fingerprints. Stromatoxin-1 (100 nM) increased the spontaneous phasic contraction amplitude, muscle force, and tone in isolated UBSM strips. However, stromatoxin-1 (100 nM) had no effect on the UBSM contractions induced by depolarizing agents such as KCl (20 mM) or carbachol (1 μM). This indicates that, under conditions of sustained membrane depolarization, the KV channels sensitive to stromatoxin-1 have no further contribution to the membrane excitability and contractility. Stromatoxin-1 (100 nM) increased the amplitude of the electrical field stimulation-induced contractions, suggesting also a role for these channels in neurogenic contractions. RT-PCR experiments on freshly isolated UBSM cells showed mRNA expression of KV2.1, KV2.2, and KV9.3, but not KV4.2 channel subunits. Protein expression of KV2.1 and KV2.2 channels was detected using Western blot and was further confirmed by immunocytochemical detection in freshly isolated UBSM cells. These novel findings indicate that KV2.1 and KV2.2, but not KV4.2, channel subunits are expressed in rat UBSM and play a key role in opposing both myogenic and neurogenic UBSM contractions.

scholarly journals The Effect of Aconitine on the Giant Axon of the Squid

1964 ◽  
Vol 47 (4) ◽  
pp. 719-733 ◽  
Author(s):  
W. H. Herzog ◽  
R. M. Feibel ◽  
S. H. Bryant
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Giant Axon ◽  
Membrane Resistance ◽  
Repetitive Stimulation ◽  
Resting Membrane Potential ◽  
Sustained Activity ◽  
Frequency Of Stimulation ◽  
Sodium And Potassium

In the giant axon of Loligo pealii, "aconitine potent" Merck added to the bath (10-7 to 1.25 x 10-6 gm/ml) (a) had no effect on resting membrane potential, membrane resistance and rectification, membrane response to subthreshold currents, critical depolarization, or action potential, but (b) on repetitive stimulation produced oscillations of membrane potential after the spike, depolarization, and decrease of membrane resistance. The effect sums with successive action potentials; it increases with concentration of aconitine, time of exposure, and frequency of stimulation. When the oscillations are large enough and the membrane potential is 51.6 ± SD 1.5 mv a burst of self-sustained activity begins; it usually lasts 20 to 70 sec. and at its end the membrane potential is 41.5 ± SD 1.9 mv. Repolarization occurs with a time constant of 2.5 to 11.1 min. Substitution of choline for external sodium after a burst hyperpolarizes the membrane to -70 mv, and return to normal external sodium depolarizes again beyond the resting membrane potential. The effect of aconitine on the membrane is attributed to an increase of sodium and potassium or chloride conductances following the action potential.

scholarly journals Substance P modulates nicotinic responses of intracardiac neurons to acetylcholine in the guinea pig

2001 ◽  
Vol 281 (6) ◽  
pp. R1792-R1800 ◽  
Author(s):  
Lili Zhang ◽  
John D. Tompkins ◽  
John C. Hancock ◽  
Donald B. Hoover
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Action Potential ◽  
Action Potentials ◽  
Neuronal Excitability ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Local Pressure ◽  
Slow Depolarization ◽  
Intracardiac Neurons

—Application of substance P (SP) to intracardiac neurons of the guinea pig causes slow depolarization and increases neuronal excitability. The present study was done to determine the influence of SP on fast excitatory responses of intracardiac neurons to ACh. Intracellular recording methods were used to measure responses of intracardiac neurons in whole mount preparations of atrial ganglionated nerve plexus from guinea pig hearts. Local pressure ejection of 100 μM SP (1 s) from a glass micropipette caused slow depolarization of all neurons ( n = 38) and triggered action potential generation in 47% of the cells tested. Bath application of SP (0.5–100 μM) caused a dose-dependent depolarization of intracardiac neurons but rarely evoked action potentials, even at the highest concentration. However, such treatment with SP enhanced nicotinic responses evoked by local pressure ejections of ACh (10 mM, 10- to 100-ms duration) in 77% of intracardiac neurons studied ( n = 52). A significant increase in amplitude of ACh-evoked fast depolarization occurred during treatment with 0.5 μM SP (13.0 ± 1.8 mV for control vs. 17.7 ± 1.9 mV with SP present, n = 7, P = 0.019). At higher concentrations of SP, enhancement of the response to ACh resulted mainly in action potential generation. However, responses to ACh were attenuated by SP in 15% of the intracardiac neurons studied. This attenuation occurred primarily during exposure to 10 and 100 μM SP and was manifest as a reduction in amplitude of nicotinic fast depolarization or inhibition of ACh-evoked action potentials. These findings support the conclusion that SP could function as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig.

Ratiometry of transmembrane voltage-sensitive fluorescent dye emission in hearts

2000 ◽  
Vol 279 (3) ◽  
pp. H1421-H1433 ◽  
Author(s):  
Stephen B. Knisley ◽  
Robert K. Justice ◽  
Wei Kong ◽  
Philip L. Johnson
Keyword(s):  
Membrane Potential ◽  
Action Potentials ◽  
Signal To Noise Ratio ◽  
Green Emission ◽  
Motion Artifacts ◽  
Resting Membrane Potential ◽  
Baseline Drift ◽  
Fluorescence Measurements ◽  
Transmembrane Voltage ◽  
Voltage Dependent

Transmembrane voltage-sensitive fluorescence measurements are limited by baseline drift that can obscure changes in resting membrane potential and by motion artifacts that can obscure repolarization. Voltage-dependent shift of emission wavelengths may allow reduction of drift and motion artifacts by emission ratiometry. We have tested this for action potentials and potassium-induced changes in resting membrane potential in rabbit hearts stained with di-4-ANEPPS [Pyridinium, 4-(2-(6-(dibutylamino)-2-naphthalenyl) ethenyl)-1-(3-sulfopropyl)-, hydroxide, inner salt] using laser excitation (488 nm) and a two-photomultiplier tube system or spectrofluorometer (resolution of 500–1,000 Hz and <1 mm). Green and red emissions produced upright and inverted action potentials, respectively. Ratios of green emission to red emission followed action potential contours and exhibited larger fractional changes than either emission alone ( P < 0.001). The largest changes and signal-to-noise ratio (signal/noise) were obtained with numerator wavelengths of 525–550 nm and denominator wavelengths of 650–700 nm. Ratiometry lessened drift 56–66% ( P < 0.015) and indicated decreases in resting membrane potential. Ratiometry lessened motion artifacts and increased magnitudes of deflections representing phase-zero depolarizations relative to total deflections by 123–188% in intact hearts ( P < 0.02). Durations of action potentials at different pacing rates, temperatures, and potassium concentrations were independent of whether they were measured ratiometrically or with microelectrodes ( P ≥ 0.65). The ratiometric calibration slope was 0.017/100 mV and decreased with time. Thus emission ratiometry lessens the effects of motion and drift and indicates resting membrane potential changes and repolarization.

Sodium dependence of the thyrotrophin-induced depolarization in cultured porcine thyroid cells

1986 ◽  
Vol 108 (2) ◽  
pp. 225-230 ◽  
Author(s):  
T. A. Hambleton ◽  
J. R. Bourke ◽  
G. J. Huxham ◽  
S. W. Manley
Keyword(s):  
Membrane Potential ◽  
Action Potentials ◽  
Potassium Concentration ◽  
Sodium Current ◽  
Resting Membrane Potential ◽  
Thyroid Cell ◽  
Free Medium ◽  
Thyroid Cells ◽  
Voltage Dependent ◽  
Sodium And Potassium

ABSTRACT Cultured porcine thyroid cells exhibit a resting membrane potential of about − 73 mV and depolarize to about − 54 mV on exposure to TSH. The depolarizing response to TSH was preserved in a medium consisting only of inorganic salts and buffers, but was abolished in sodium-free medium, demonstrating dependence on an inward sodium current. Increasing the potassium concentration of the medium resulted in a reduction in the resting membrane potential of 60 mV per tenfold change in potassium concentration, and a diminished TSH response. A hyperpolarizing TSH response was observed in a sodium- and bicarbonate-free medium, indicating that a hyperpolarizing ion current (probably carried by potassium) was also enhanced in the presence of TSH. Tetrodotoxin blocked the TSH response. We conclude that the response of the thyroid cell membrane to TSH involves increases in permeability to sodium and potassium, and that the thyroid membrane ion channels bear some similarity to the voltage-dependent sodium channels of excitable tissues, despite the absence of action potentials in the thyroid. J. Endocr. (1986) 108, 225–230

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